Project/Area Number |
04670202
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Experimental pathology
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Research Institution | Gifu University |
Principal Investigator |
MORI Hideki Gifu University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (70021433)
|
Co-Investigator(Kenkyū-buntansha) |
SUGIE Shigeyuki Hospital associated with Gifu University School of Medicine, Department of Patho, 医学部・附属病院, 助手 (60187648)
YOSHIMI Naoki Gifu University School of Medicine, Department of Pathology, Instructor, 医学部, 講師 (30166996)
TANAKA Takuji Gifu University School of Medicine, Department of Pathology, Associate professor, 医学部, 助教授 (40126743)
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Project Period (FY) |
1992 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
Keywords | Hydroxyanthraquinone / Ulcerative colitis / Large bowel cancer / Rat / Mouse / Cell proliferation / Tumor promotion / Cytokines / 1.2-dimethylhydrazine / 結腸腫瘍 / 肛門腫瘍 / ハムスター / BrdU / 大腸粘膜 / ODC活性 / 陰高長 / 潰瘍性病変 / メラノーシス |
Research Abstract |
1) Development of the model for ulcerative colitis - large bowel cancer : Dietary administration of l-hydroxyanthraquinone (HA*) (1%) to rats for approximately 460 days was done. Twenty five rats out of 29 effective animals developed large bowel neoplasms (adenoma or adenocarcinoma). All of these effective rats also developed some pathological changes which are often seen in ulcerative colitis patients. They were crypt abscess, melanosis, erosion or regenerative epithels. These results indicate that HA* induces simultaneously pathological changes resembling those appeared in the case of ulcerative colitis and neoplasms. 2) Cell kinetic analysis of proliferative epithelial cells in rats given HA* : Sequential observation of the large bowels of rats exposed to HA* (1%) by sacrifice of animals at 4, 8 or 12 months after the start of tye dietary exposure. Thickness, number of cells constituting crypt, labelling indices of BrdU in the crypt cells, ODC activity and appearance of the changes s
… More
uch as erosion, crypt abscess of the large bowels of rats with HA* were respectively greater than those of control animals. Each of the biomarkers became greater responding to the exposure-time of HA*. 3) Tumor-promotive effect of 1, 8-dihydroxianthraquinone (danthron) in the large of mice : Modifying effect of danthron on dimethylhydrazine (DMH)-induced large bowel carcinogenesis in mice was examined. Incidence of colon neoplasms (adenoma or adenocarcinoma) in mice given DMH together with danthron was significantly higher than that of mice exposed to DMH alone. ODC activity of the large bowel of mice given danthron was much greater than that of controls. Expression of cytokines, TNF-a and IL-la in the large bowel carcinogenesis by MAM acetate and HA* : Expression of the cytokines was examined by RT-PCR method. Expression of the cytokines in the colon neoplasms was stronger than in non-neoplastic mucosa. That of cytokines in the colon mucosa given both agents or either of the agents was aloso greater than in controls. The synergistic effects of HA* with MAM acetate might be related to the biological effects of the cytokines expressed in the inflammatory conditioned generated by HA*. Less
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